The neural crest is a multipotent stem cell-like population, unique to vertebrates, that is essential for normal craniofacial morphogenesis. These cells contribute to a wide variety of derivatives, including the craniofacial skeleton and cartilage, sensory and autonomic ganglia of the peripheral nervous system, and pigmentation of the skin. Neural crest progenitors arise at the neural plate border, between neural and non- neural ectoderm, and, after neurulation, reside within the dorsal aspect of the future central nervous system, the neural tube. Neural crest cells then undergo an epithelial-to-mesenchymal transition (EMT) to exit the neural tube, and migrate extensively at times to distant locations. Once they reach their destination, neural crest cells cease their migratory program and differentiate into a wide range of derivatives. The neural crest is indispensable for the development of the face? genetic defects affecting neural crest generation, migration, proliferation, or differentiation, result in numerous diseases and malformations affecting the face, e.g. Treacher Collins syndrome, DiGeorge syndrome, and cleft palate to name a few. Thus, there is a need for basic scientific knowledge regarding the precise mechanisms underlying neural crest development. To this end, the Specific Aims of this Proposal seek to use loss-of-function experiments to: 1) Characterize the role of a gene, draxin, in cranial neural crest fate specification and EMT/migration by RNA sequencing and time-lapse confocal microscopy; and 2) Identify the signaling pathway(s) with which draxin interacts to regulate cranial neural crest development, by fluorescent reporter expression and in situ protein-protein interaction assays. The goal of this Proposal is to identify the mechanism by which draxin regulates cranial neural crest EMT and migration during development. Thus, the results of this Proposal will significantly enhance our understanding of the regulation of cranial neural crest EMT and migration, providing new scientific avenues for translational research applications in the treatment of craniofacial defects.

Public Health Relevance

PUBLIC HEALTH RELEVANCE: Defects in cranial neural crest development lead to a variety of craniofacial diseases and malformations affecting the face, e.g. Treacher Collins syndrome, DiGeorge syndrome, and cleft palate to name a few. In this project, I will investigate during development the function of a gene, draxin, to shed important new light on the mechanisms governing cranial neural crest fate specification and migration, which will provide important clues for understanding the etiology of craniofacial abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE026355-02
Application #
9303766
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2016-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Hutchins, Erica J; Bronner, Marianne E (2018) Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT. J Cell Biol 217:3683-3697
Hutchins, Erica J; Kunttas, Ezgi; Piacentino, Michael L et al. (2018) Migration and diversification of the vagal neural crest. Dev Biol :